Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis

Alexandra Argyriou, Marc H. Wadsworth, Adrian Lendvai, Stephen M. Christensen, Aase H. Hensvold, Christina Gerstner, Annika Vollenhoven, Kellie Kravarik, Aaron Winkler, Vivianne Malmström and Karine Chemin ()
Additional contact information
Alexandra Argyriou: Karolinska University Hospital
Marc H. Wadsworth: Inflammation & Immunology Research Unit, Pfizer Inc.
Adrian Lendvai: Karolinska University Hospital
Stephen M. Christensen: Inflammation & Immunology Research Unit, Pfizer Inc.
Aase H. Hensvold: Karolinska University Hospital
Christina Gerstner: Karolinska University Hospital
Annika Vollenhoven: Karolinska University Hospital
Kellie Kravarik: Inflammation & Immunology Research Unit, Pfizer Inc.
Aaron Winkler: Inflammation & Immunology Research Unit, Pfizer Inc.
Vivianne Malmström: Karolinska University Hospital
Karine Chemin: Karolinska University Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4+ T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4+ T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (TPH) states and a cytotoxic CD4+ T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13high TPH CD4+ T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, TPH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13high TPH CD4+ T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two TPH clusters and effector CD4+ T cells. Our study provides comprehensive immunoprofiling of the synovial CD4+ T cell subsets in ACPA+ and ACPA- RA.

Date: 2022
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DOI: 10.1038/s41467-022-31519-6

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